Deconstructing inflammatory memory across tissue set points using cell circuit motifs

Kwong, Andrew C.; Ordovas-Montanes, Jose

doi:10.1016/j.jaci.2024.09.014

Journal of Allergy and Clinical Immunology

2024

DOI: 10.1016/j.jaci.2024.09.014

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Deconstructing inflammatory memory across tissue set points using cell circuit motifs

Andrew C. Kwong,

Jose Ordovas-Montanes

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2024

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Redefining Roles: A Paradigm Shift in Tryptophan–Kynurenine Metabolism for Innovative Clinical Applications

Tanaka,

Szabó,

Vécsei

2024

IJMS

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The tryptophan–kynurenine (KYN) pathway has long been recognized for its essential role in generating metabolites that influence various physiological processes. Traditionally, these metabolites have been categorized into distinct, often opposing groups, such as pro-oxidant versus antioxidant, excitotoxic/neurotoxic versus neuroprotective. This dichotomous framework has shaped much of the research on conditions like neurodegenerative and neuropsychiatric disorders, as well as cancer, where metabolic imbalances are a key feature. The effects are significantly influenced by various factors, including the concentration of metabolites and the particular cellular milieu in which they are generated. A molecule that acts as neuroprotective at low concentrations may exhibit neurotoxic effects at elevated levels. The oxidative equilibrium of the surrounding environment can alter the function of KYN from an antioxidant to a pro-oxidant. This narrative review offers a comprehensive examination and analysis of the contemporary understanding of KYN metabolites, emphasizing their multifaceted biological functions and their relevance in numerous physiological and pathological processes. This underscores the pressing necessity for a paradigm shift in the comprehension of KYN metabolism. Understanding the context-dependent roles of KYN metabolites is vital for novel therapies in conditions like Alzheimer’s disease, multiple sclerosis, and cancer. Comprehensive pathway modulation, including balancing inflammatory signals and enzyme regulation, offers promising avenues for targeted, effective treatments.

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Redefining Roles: A Paradigm Shift in Tryptophan–Kynurenine Metabolism for Innovative Clinical Applications

Tanaka,

Szabó,

Vécsei

2024

IJMS

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Deconstructing inflammatory memory across tissue set points using cell circuit motifs

Cited by 1 publication

References 125 publications

Redefining Roles: A Paradigm Shift in Tryptophan–Kynurenine Metabolism for Innovative Clinical Applications

Redefining Roles: A Paradigm Shift in Tryptophan–Kynurenine Metabolism for Innovative Clinical Applications

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